In 10 healthy male volunteers breathing 100% oxygen, we determined the effect of four intravenous dose levels of fentanyl (0.0015, 0.003, 0.006 and 0.009 mg/kg) and two of fentanyl plus droperidol (i.e., Innovar, 0.003 and 0.006 mg/kg of fentanyl with 2.5 mg of droperidol for each 0.05 mg of fentanyl) on PECO2 and the slope of the ventilatory response to imposed increases in PECO2. All doses of fentanyl and fentanyl plus droperidol depressed the slope and shifted the curve to the right. Depression was dose related and was maximum 5 minutes after administration. The slope returned to control by 2 hours postinjection even at the highest narcotic dose. However, the rightward shift of the CO2 response curve require 4 hours to return to control. Droperidol added to fentanyl did not increase or prolong the respiratory depression seen with fentanyl alone at equivalent dose levels. Nausea and emesis occurred more frequently with fentanyl alone and orthostatic hypotension occurred more frequently with droperidol plus fentanyl. Dysphoria was a prominent consequence of fentanyl plus droperidol administration.